The cells involved in bone resorption and bone formation, i.e. osteoclasts and osteoblasts, will be studied in animal models and in organ culture. Their activity will be assessed by quantitative ultrastructural morphology and these data will be correlated with biochemical data in the same animal or on the same tissue. We will test the effects of vitamin D metabolites and interactions with parathyroid hormone in rats. We will study a variety of metabolic conditions in rats and test the effects of diphosphonates. Non-osteoclastic bone resorption will be investigated in a rat model. Bone formation and mechanisms of stimulation by insulin and inhibition by parathyroid hormone will be studied in organ culture.